chemotherapy mechanism of action

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pdnguyen
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82144
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chemotherapy mechanism of action
Updated:
2011-04-27 10:16:31
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chemotherapy mechanism action
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chemotherapy mechanism of action
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  1. Methotrexate
    • Competitively inhibits DHFR preventing FH4 formation
    • G1/S
  2. Leucovorine
    Bypasses blocked reductase enzyme --> replenish folate pool
  3. 5-Fluorouracil
    • 5-FUTP - block RNA processing
    • 5-FdUMP --> inhibit thymidylate synthase --> inhibit DNA synthesis
    • G1/S
  4. 5-Fluorodeoxyuridine
    • converted to 5-FU
    • 5-FdUMP --> inhibit thymidylate synthase --> inhibits DNA synthesis
  5. Capecitabine
    • converted to 5-FU
    • inhibit thymidylate synthase --> inhibit DNA synthesis
  6. Cytarabine
    • phosphorylated --> araCTP --> decrease DNA synthesis
    • competitive inhibitor --> DNA polymerase --> inhibits chain elongation and ligation
    • S
  7. gemcitabine
    • diphosphate --> inhibits ribonucleotide reductase --> inhibit DNA synthesis
    • triphosphate --> inhibits DNA polymerases --> arrests DNA synthesis and induces apoptosis
  8. 6-Thioguanine and 6-mercaptopurine
    • substrates for HGPRT + SAM + TPMT --> methylation (inhibition of purine synthesis)
    • blocks formation of AMP
    • non-functional RNA and DNA
  9. Fludarabine
    dephosphorylated --> phosphorylated --> triphosphate --> inhibits DNA polymerase and ribonucleotide reductase --> decrease DNA synthesis
  10. Cladribine
    phosphorylated --> incorporated into DNA --> interfere with DNA repair.
  11. hydroxyurea
    • inhibits ribonucleotide reductase --> inhibit DNA synthesis
    • G1/S
  12. vinca alkaloids
    • blocks ability of tubulin to polymerize --> prevent assembly
    • M
  13. taxanes
    • bind to already formed spindles --> prevent dissembly
    • M
  14. anthracyclines
    • DNA intercalation
    • ROS
    • Topoisomerase II inhibition
    • S phase
  15. Dactinomycin
    • intercalates between G-C
    • inhibit RNA polymerase
    • M
  16. Bleomycin
    • DNA intercalation
    • hydroxyl free radicals formation
  17. epipodophyllotoxins
    topoisomerase II inhibition
  18. camptocethin
    topoisomerase I inhibition
  19. alkylating agents
    • more acidic G
    • destabilize G
    • bi-functional agent
  20. cyclophosphamide
    hydroxylation --> acrolein + phosphoramide mustard
  21. iforsfamide
    Hydrolysis --> acrolein + ifosfamide mustard
  22. nitrosoureas
    DNA cross-links
  23. procarbazine
    oxidation --> diazomethane --> guanine methylation
  24. triazines
    N-demethylation --> MTIC --> methylcarbonium --> guanine methyl alkylation
  25. ThioTEPA
    desulfuration --> TEPA
  26. Platinum complexes
    Lose Cl and forms cross-links

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